Endodontics is a field of dentistry concerned with the biology and pathology of the dental pulp and periapical tissues. Endodontic treatment employs a set of techniques, such as chemomechanical debridement, irrigation, drainage of hard and soft tissue, trephination, and antimicrobial therapy, with the goal of avoiding the extraction of a damaged, infected or diseased tooth.
Normal vital pulp is sterile, and the role of bacterial infection in the pathogenesis of pulpal and periapical disease is well established. Infected or necrotic pulpal tissue renders the pulp chamber and root canal a potential reservoir of bacteria, and disinfection of the tooth is one of the primary justifications for the chemomechanical aspects of root canal therapy. Recent data demonstrate a high incidence of root canal failure in necrotic teeth treated in a single visit, attributed to bacteria remaining in complex anatomical spaces such as accessory canals, fins, deltas and isthmuses (Sjorgen et al., Int. Endo. J., 30:297-306 (1997)). Other studies have reported the ability of bacteria to migrate into dentinal tubules and survive therein (Nagaoka et al., J. Endodon., 21:70-73 (1995)). It is speculated that the success rate of endodontic treatment could be 26% higher if the root canal is successfully disinfected prior to the final restoration (Sjorgen et al., Int. Endo. J., 30:297-306 (1997)).
Root canal infections are characterized as polymicrobial infections which tend to be dominated by anaerobic bacteria. As a group, the common endodontic microbes associated with treatment failure include F. nucleatum, P. intermedia, P. micros, S. intermedius, P. endodontlis, P. gingivalis, P. melaninogenica, E. lentum, V. parvula, S. sanguis, P. buccae, P. oralis, and P. acnes. (Haapasalo, FEMS Immunol. and Medical Micro. 6:213-217 (1993) and Sundqvist, J. Endodon., 7:257-262 (1992)).
Post-operative periapical pain and interappointment flare-ups are also routinely attributed to the presence of bacteria, and/or their by-products, within the root canal. Typically, an initial bacterial infection triggers a host-mediated inflammatory response, the consequences of which underlie the flare-up patient""s clinical symptoms. It has been reported that bacteria surviving instrumentation and irrigation proliferate rapidly in empty root canals (Bystrom and Sundqvist, Oral. Surg. Oral. Med. Oral Pathol., 55:307-312 (1983)), and there is a positive correlation between the number of bacteria present in a root canal and the incidence of inter-appointment flare-ups. The presence of black-pigmented, gram negative anaerobes in the root canal usually accompanies patient complaints of pain, swelling, and tenderness to percussion (Haapasalo, FEMS Immunol. and Medical Micro., 6:213-217 (1993)). Thus, the successful elimination of bacteria from root canals may lower the incidence of flare-ups.
Antibiotics have historically been used as an adjunct to endodontic treatment either by systemic or local administration. Currently, antibiotic treatment for root canal infections and exacerbations is limited to systemic administration. Thus, in light of the established correlations between the primary and secondary effects of bacterial presence and the incidence of both interappointment flare-ups and treatment failure, there is a clear need for an efficacious method of delivering and sustaining substantial concentrations of intracanal medicaments, particularly antibiotics.
During the 1950""s a polyantibiotic paste (PBSC) was devised for use as an intracanal medicament (Grossman, L. I., J. Amer. Dent. Assoc., 43:265-278 (1951)). PBSC consisted of penicillin to target gram positive organisms, bacitracin for penicillin-resistant strains, streptomycin for gram negative organisms and caprylate sodium to target yeast, all suspended in a silicone vehicle. Although, clinical evaluation suggested that polyantibiotic paste conferred a therapeutic benefit (fewer treatments to achieve a negative culture) the composition was ineffective against anaerobic species (which are now appreciated as the dominant species responsible for treatment failure). In 1975 the Food and Drug Administration (FDA) banned PBSC for endodontic use primarily because of the risks of sensitization and allergic reactions attributed to the penicillin. This underscores the importance of improving historical endodontic methodologies, particularly local delivery methods, in light of contemporary knowledge and technological advances.
The invention relates to endodontic fibers comprising a biocompatible polymer vehicle which is permeable to medicaments, or combinations of medicaments, dispersed, e.g., homogeneously, therein. Such fibers can be used, for example, in a method for the local delivery and sustained release of medicaments to periodontal or intracanal treatment sites. Endodontic fibers of this invention include modified periodontal fibers and intracanal fibers.
One embodiment of the invention relates to modified periodontal fibers suitable for delivery of medicaments to intracanal treatment sites. These first generation endodontic fibers, referred to herein as xe2x80x9cmodified peridontal fibersxe2x80x9d, represent an adaptation of an ethylene vinyl acetate delivery vehicle (see U.S. Pat. No. 4,764,377 and U.S. Pat. No. 4,892,736) previously developed to administer therapeutic agents during the course of periodontal treatment (Gilad, xe2x80x9cDevelopment of a Clindamycin Impregnated EVA fiber as an Intracanal Medicament in Endodontic Therapy,xe2x80x9d Master of Medical Sciences Thesis, Harvard University School of Dental Medicine, defended Apr. 2, 1998, and Gilad, et al., xe2x80x9cDevelopment of a Clindamycin-Impregnated Fiber as an Intracanal Medication in Endodontic Therapy,xe2x80x9d Journal of Endodontics, 25(11):722-727 (1999), the entire teachings of which are incorporated herein by reference). Specifically, the periodontal fibers have been modified to confer properties which allow the use of the fiber within an intracanal treatment site, e.g., to confer specific physical characteristics such as form and consistency. In one embodiment, the modification comprises the treatment of the periodontal fiber with an agent such as a biocompatible refrigerant spray (e.g., Endo Ice).
In an alternative embodiment, the invention also relates to a second generation endodontic fiber, referred to herein as an xe2x80x9cintracanal fiber,xe2x80x9d which can be specifically designed for use in intracanal delivery methods, thereby obviating the need to modify a peridontal fiber for use in intracanal sites. Such design can include an alteration in the composition and/or ratio of components of the fiber. For example, as described herein, it has been discovered that an ethylene vinyl acetate (EVA) fiber containing less than about 20% vinyl acetate is suitable for use as an intracanal fiber. In a preferred embodiment, the EVA fiber contains less than about 20%, preferably less than about 15% and more preferably less than about 10% vinyl acetate. In one embodiment, the EVA fiber contains about 9.3% vinyl acetate. In a preferred embodiment, the intracanal fiber has a diameter of less than about 0.5 mm. In one embodiment the intracanal fiber has a diameter of about 0.3 mm.
The invention is demonstrated herein using clindamycin/ethylene vinyl acetate (EVA) fibers; however, this example is not intended to limit the scope of the invention in any way. For example, the contemplated intracanal fiber can be formulated to have a polymeric composition, surface tackiness, stiffness, glass transition temperature, and/or diameter selected to confer characteristics compatible with placement within the root canal. Although the second generation intracanal fiber is particularly adapted for intracanal use, other (i.e., non-intracanal) uses of this fiber are also envisioned. For example, the intracanal fiber can also be used for periodontal treatment.
In addition, the choice of medicament and the dose at which it is incorporated into the disclosed endodontic fibers (e.g., modified peridontal fibers or intracanal fibers) are optimized to produce a fiber that is most likely to achieve the desired therapeutic effect. The intracanal fibers exemplified and contemplated herein are ideally suited for the local delivery and sustained release of intracanal medicaments and thus enable numerous intracanal delivery methods.
In one aspect of endodontic use, endodontic fibers (e.g., modified peridontal fibers or intracanal fibers) are utilized for the intracanal delivery and sustained release of antibiotics predicted to be efficacious for the treatment of an established endodontic bacterial infection. The goal of the intracanal delivery of antibiotics in this context is to achieve a sufficient drug concentration and duration of contact, to effect inhibition (e.g., partial or complete inhibition) of all bacterial growth within the pulp chamber and root canal, thereby obviating the need for systemic antibiotic administration. Ultimately, the ability to successfully treat established bacterial infections will reduce endodontic treatment failures.
In an alternative embodiment, an intracanal delivery method using endodontic fibers of the invention is utilized prophylactically to disinfect a root canal receiving endodontic treatment prior to the application of a final restoration. In this context, the local delivery method is employed to eradicate any residual bacteria which were not removed by the chemomechanical preparation of the canal. More specifically, the purpose of this method of delivery is to suppress bacterial growth, particularly the proliferation of black-pigmented, gram negative organisms within the root canal. Such prophylaxis can reduce the level of patient pain due to inflammation and the occurrence of interappointment flare-ups, and ultimately minimize the risk of treatment failures.
In other embodiments of the invention, endodontic fibers described herein can be used to deliver alternative intracanal medicaments necessitated by a course of endodontic treatment. For example, in an effort to attenuate a host-mediated inflammatory response resulting from the presence of bacterial by-products in periapical tissues, an anti-inflammatory agent, either alone or in combination with an antibiotic, can be incorporated into the endodontic fiber.